ADCK1 activates the β-catenin/TCF signaling pathway to promote the growth and migration of colon cancer cells

AbstractAs a result of mutations in the upstream components of the Wnt/β-catenin signaling pathway, this cascade is abnormally activated in colon cancer. Hence, identifying the activation mechanism of this pathway is an urgent need for the treatment of colon cancer. Here, we found an increase in ADCK1 (AarF domain-containing kinase 1) expression in clinical specimens of colon cancer and animal models. Upregulation of ADCK1 expression promoted the colony formation and infiltration of cancer cells. Downregulation of ADCK1 expression inhibited the colony formation and infiltration of cancer cells, in vivo tumorigenesis, migration, and organoid formation. Molecular mechanistic studies demonstrated that ADCK1 interacted with TCF4 (T-cell factor 4) to activate the β-catenin/TCF signaling pathway. In conclusion, our research revealed the functions of ADCK1 in the development of colon cancer and provided potential therapeutic targets.

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MicroRNA 375 regulates proliferation and migration of colon cancer cells by suppressing the CTGF-EGFR signaling pathway

International Journal of Cancer ◽

10.1002/ijc.30861 ◽

2017 ◽

Vol 141 (8) ◽

pp. 1614-1629 ◽

Cited By ~ 26

Author(s):

Khondoker Jahengir Alam ◽

Ji-Su Mo ◽

Seol-Hee Han ◽

Won-Cheol Park ◽

Hun-Soo Kim ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Colon Cancer Cells ◽

Egfr Signaling ◽

Egfr Signaling Pathway ◽

And Migration ◽

Proliferation And Migration

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Butyrate suppresses proliferation and migration of RKO colon cancer cells though regulating endocan expression by MAPK signaling pathway

Food and Chemical Toxicology ◽

10.1016/j.fct.2013.10.028 ◽

2013 ◽

Vol 62 ◽

pp. 892-900 ◽

Cited By ~ 18

Author(s):

Li Zuo ◽

Man Lu ◽

Qing Zhou ◽

Wei Wei ◽

Yuan Wang

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Mapk Signaling ◽

Mapk Signaling Pathway ◽

Colon Cancer Cells ◽

And Migration ◽

Proliferation And Migration

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Nrf3 Promotes 5-FU Resistance in Colorectal Cancer Cells via the NF-κB/BCL-2 Signaling Pathway In Vitro and In Vivo

Journal of Oncology ◽

10.1155/2021/9355555 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Bi-Qing Cai ◽

Wan-Meng Chen ◽

Jia Zhao ◽

Wei Hou ◽

Jian-Cai Tang

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Colon Cancer Cells ◽

Tumor Drug Resistance ◽

Colorectal Cancer Cells ◽

Cancer Tissues ◽

The Relationship

Increasing evidence indicates that nuclear factor, erythroid 2-like 3 (Nrf3) is connected with tumorigenesis. However, the relationship between Nrf3 and tumor drug resistance remains elusive. In this study, we investigated the effect and mechanism of action by which Nrf3 regulated the sensitivity of colon cancer cells to 5-fluorouracil (5-FU). We found Nrf3 was significantly increased in colon cancer tissues. Furthermore, we observed that Nrf3 knockdown and overexpression can significantly affect the sensitivity of colon cancer cells to 5-FU in vitro and in vivo. Moreover, Nrf3 promoted the expression of RELA, P-RELA, and BCL-2. Inhibition of NF-κB partly reversed the effects of Nrf3 overexpression, resulting in the resistance of colon cancer cells to 5-FU. Overall, the study revealed that Nrf3 was connected to the sensitivity of colon cancer cells to 5-FU, and its possible mechanism was related to the NF-κB signaling pathway, which provided a new target for overcoming the resistance of colon cancer cells to 5-FU.

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Cinobufacini Inhibits Colon Cancer Invasion and Metastasis via Suppressing Wnt/β-Catenin Signaling Pathway and EMT

The American Journal of Chinese Medicine ◽

10.1142/s0192415x20500354 ◽

2020 ◽

Vol 48 (03) ◽

pp. 703-718 ◽

Cited By ~ 3

Author(s):

Jie Wang ◽

Han Cai ◽

Qiaoli Liu ◽

Yue Xia ◽

LiKai Xing ◽

...

Keyword(s):

Colon Cancer ◽

Signaling Pathway ◽

Cancer Invasion ◽

In Vivo Studies ◽

Colon Cancer Cells ◽

Invasion And Metastasis ◽

Invasion And Migration ◽

And Migration

Cinobufacini is a well-known Chinese medicine extracted from Venenum Bufonis, also called Chan Su. It has been used clinically for various cancers, including colon cancer. However, the function of Cinobufacini on colon cancer invasion and metastasis, and its underlying molecular mechanism, is still not clear. In this study, we investigated the function and mechanism of Cinobufacini on colon cancer invasion and metastasis both in vitro and in vivo studies. Human colon cancer cells were cultured. CCK assay was used to detect the effect of Cinobufacini on colon cancer cells proliferation. The invasion and migration abilities were observed by transwell assays, and the expression of invasion and migration related genes MMP2, MMP9, and epithelial-to-mesenchymal transition (EMT) relate genes were observed by Western blot assays. An orthotopic xenograft model in nude mice was established using colon cancer HCT116 cells, and the function of Cinobufacini on colon cancer invasion and metastasis were observed in vivo. We found Cinobufacini significantly inhibited colon cancer cell proliferation in a dose/time-dependent manner; the invasion and migration abilities of colon cancer were decreased after treated with Cinobufacini. The metastasis and EMT related genes MMP9, MMP2, N-cadherin and Snail were obviously down-regulated, while the expression of E-cadherin was up-regulated after treatment with Cinobufacini. The Wnt/[Formula: see text]-catenin signaling pathway related genes were observed using WB,and results show that the expression of [Formula: see text]-catenin, wnt3a, c-myc, cyclin D1, and MMP7 were all down-regulated after being treated with cinobufacini, while the expression of APC was up-regulated. In vivo studies of the volume and weight of orthotopic xenograft tumors showed significantly shrinkage in the Cinobufacini group compared to the control group. The enterocoelia and liver metastasis tumors were significantly decreased, and the expression of MMP9, MMP2, and [Formula: see text]-catenin were also down-regulated, while E-cadherin was up-regulated in vivo after the treatment with Cinobufacini. Our data proves that Cinobufacini can inhibit colon cancer invasion and metastasis both in vitro and in vivo; the mechanism is related by suppressing the Wnt/[Formula: see text]-catenin signaling pathway and then inhibiting the EMT of CRC.

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miR-218 inhibits the invasion and migration of colon cancer cells by targeting the PI3K/Akt/mTOR signaling pathway

International Journal of Molecular Medicine ◽

10.3892/ijmm.2015.2126 ◽

2015 ◽

Vol 35 (5) ◽

pp. 1301-1308 ◽

Cited By ~ 42

Author(s):

XIANGLIANG ZHANG ◽

HUIJUAN SHI ◽

HONGSHENG TANG ◽

ZHIYUAN FANG ◽

JIPING WANG ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Mtor Signaling ◽

Colon Cancer Cells ◽

Mtor Signaling Pathway ◽

Invasion And Migration ◽

And Migration

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Transgelin interacts with PARP1 in human colon cancer cells

10.21203/rs.3.rs-16964/v3 ◽

2020 ◽

Author(s):

Zhen-xian Lew ◽

Hui-min Zhou ◽

Yuan-yuan Fang ◽

Zhen Ye ◽

Wa Zhong ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Cellular Localization ◽

Actin Binding ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

Key Genes

Abstract Background: Transgelin, an actin-binding protein, is associated with cytoskeleton remodeling. Findings from our previous studies demonstrated that transgelin was up-regulated in node-positive colorectal cancer (CRC) versus node-negative disease. Over-expression of TAGLN affected the expression of 256 downstream transcripts and increased the metastatic potential of colon cancer cells in vitro and in vivo. This study aims to explore the mechanisms through which transgelin participates in the metastasis of colon cancer cells.Methods: Immunofluorescence and immunoblotting analysis were used to determine the cellular localization of endogenous and exogenous transgelin in colon cancer cells. Co-immunoprecipitation and subsequently high-performance liquid chromatography/tandem mass spectrometry were performed to identify the proteins that were potentially interacting with transgelin. The 256 downstream transcripts regulated by transgelin were analyzed with bioinformatics methods to discriminate the specific key genes and signaling pathways. The Gene-Cloud of Biotechnology Information (GCBI) tools were used to predict the potential transcription factors (TFs) for the key genes. The predicted TFs corresponded to the proteins identified to interact with transgelin. The interaction between transgelin and the TFs was verified by co-immunoprecipitation and immunofluorescence.Results: Transgelin was found to localize in both the cytoplasm and nucleus of the colon cancer cells. Approximately 297 proteins were identified to interact with transgelin. The overexpression of TAGLN led to the differential expression of 184 downstream genes. Network topology analysis discriminated seven genes, including CALM1, MYO1F, NCKIPSD, PLK4, RAC1, WAS and WIPF1 , which are mostly involved in the Rho signaling pathway. Poly (ADP-ribose) polymerase-1 (PARP1) was predicted as the unique TF for the key genes and concurrently corresponded to the DNA-binding proteins potentially interacting with transgelin. The interaction between PARP1 and transgelin in human RKO colon cancer cells was further validated by immunoprecipitation and immunofluorescence assays. Conclusions: Our results suggest that transgelin binds to PARP1 and regulates the expression of downstream key genes, which are mainly involved in the Rho signaling pathway, and thus participates in the metastasis of colon cancer.

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Astragalin Inhibits the Proliferation and Migration of Human Colon Cancer HCT116 Cells by Regulating the NF-κB Signaling Pathway

Frontiers in Pharmacology ◽

10.3389/fphar.2021.639256 ◽

2021 ◽

Vol 12 ◽

Author(s):

Min Yang ◽

Wen-Yun Li ◽

Jing Xie ◽

Zi-Lin Wang ◽

Yan-Long Wen ◽

...

Keyword(s):

Colon Cancer ◽

Signaling Pathway ◽

Human Colon ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

And Migration ◽

Hct116 Cells ◽

Proliferation And Migration

Astragalin is a flavonoid found in a variety of natural plants. It has anti-inflammatory, anti-oxidant effects and has inhibited effects against several malignant tumor cell types. However, its effects on colon cancer and the molecular mechanisms have remained to be elucidated. In this study, we evaluated the inhibitory effect of astragalin on proliferation and migration of human colon cancer HCT116 cells in vitro and in vivo. Furthermore, we elucidated the mechanism of these effects. The results showed that astragalin significantly inhibited the proliferation and diffusion of HCT116 cells by induced apoptosis (by modulation of Bax, Bcl-2, P53, caspase-3, caspase 6, caspase 7, caspase 8, caspase 9 protein express) and cell cycle arrest (by modulation of Cyclin D1, Cyclin E, P21, P27, CDK2, CDK4 protein express). Moreover, astragalin suppressed HCT116 cell migration by inhibiting the expression of matrix metalloproteinases (MMP-2, MMP-9). In addition, astragalin significantly downregulated the expression of key proteins in the NF-κB signaling pathway and inhibited the transcriptional activity of NF-κB P65 stimulated with inflammatory cytokines TNF-α, thereby inhibiting the growth of colon cancer cells in vitro. Our further investigations unveiled astragalin gavage significantly reduced the proliferation of colon cancer xenograft in nude mice, in vivo experiments showed that tumor growth was related to decreased expression of apoptotic proteins in tumor tissues and decreased activity of the NF-κB signaling pathway. In summary, our results indicated that astragalin inhibits the proliferation and growth of colon cancer cells in vivo and in vitro via the NF-κB pathway. Therefore, astragalin maybe become a potential plant-derived antitumor drug for colon cancer.

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CXCL2-CXCR2 axis mediates αV integrin-dependent peritoneal metastasis of colon cancer cells

Clinical & Experimental Metastasis ◽

10.1007/s10585-021-10103-0 ◽

2021 ◽

Author(s):

Mattias Lepsenyi ◽

Nader Algethami ◽

Amr A. Al-Haidari ◽

Anwar Algaber ◽

Ingvar Syk ◽

...

Keyword(s):

Colon Cancer ◽

Cell Adhesion ◽

Cancer Cells ◽

Cancer Cell ◽

Colon Cancer Cell ◽

Colon Cancer Cells ◽

Cancer Cell Adhesion ◽

And Migration ◽

Cxcr2 Antagonist

AbstractPeritoneal metastasis is an insidious aspect of colorectal cancer. The aim of the present study was to define mechanisms regulating colon cancer cell adhesion and spread to peritoneal wounds after abdominal surgery. Mice was laparotomized and injected intraperitoneally with CT-26 colon carcinoma cells and metastatic noduli in the peritoneal cavity was quantified after treatment with a CXCR2 antagonist or integrin-αV-antibody. CT-26 cells expressed cell surface chemokine receptors CXCR2, CXCR3, CXCR4 and CXCR5. Stimulation with the CXCR2 ligand, CXCL2, dose-dependently increased proliferation and migration of CT-26 cells in vitro. The CXCR2 antagonist, SB225002, dose-dependently decreased CXCL2-induced proliferation and migration of colon cancer cells in vitro. Intraperitoneal administration of CT-26 colon cancer cells resulted in wide-spread growth of metastatic nodules at the peritoneal surface of laparotomized animals. Laparotomy increased gene expression of CXCL2 at the incisional line. Pretreatment with CXCR2 antagonist reduced metastatic nodules by 70%. Moreover, stimulation with CXCL2 increased CT-26 cell adhesion to extracellular matrix (ECM) proteins in a CXCR2-dependent manner. CT-26 cells expressed the αV, β1 and β3 integrin subunits and immunoneutralization of αV abolished CXCL2-triggered adhesion of CT-26 to vitronectin, fibronectin and fibrinogen. Finally, inhibition of the αV integrin significantly attenuated the number of carcinomatosis nodules by 69% in laparotomized mice. These results were validated by use of the human colon cancer cell line HT-29 in vitro. Our data show that colon cancer cell adhesion and growth on peritoneal wound sites is mediated by a CXCL2-CXCR2 signaling axis and αV integrin-dependent adhesion to ECM proteins.

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